Generalized absence seizure is characterized by a brief, abrupt loss of consciousness associated with characteristic bilaterally synchronous spike and wave discharges on EEG. Both genetic rat strains and pharmacological agents (e.g. gamma-butyrolactone, GBL) have been used as models of this seizure type, but the pathogenesis and pathophysiological features remain unclear. This proposal focuses on elucidating the pathophysiology of absence seizures in both types of animal models with the use of functional MRI (fMRI). fMRI can detect a blood-oxygen-level dependent (BOLD) signal that is indicative of changes in the level of oxygen in the blood, and consequently, varies with brain activity. Performing these studies in a fully awake and conscious, restrained animal would provide not only novel information on the involvement of neuroanatomical structures, but also on the temporal sequence of events. Resources available in the Ferris laboratory will allow the use of BOLD fMRI in order to track the onset, propagation, and termination of an absence seizure in a fully awake, restrained animal during seizure activity. The temporal and spatial resolution of this technique will provide the opportunity to correlate rapidly occurring changes in neuronal activity with the corresponding neuroanatomical features. Thus, a combination of the two rat models and fMRI technology will be used to measure the time course of neuroanatomical activation in an attempt to test the hypotheses that a defined path of activation exists between the cortex and the thalamus and that a substructure of the thalamus is responsible for the initiation of seizure activity.